Current practices of dissolution testing invariably use paddle and basket apparatuses. In fact, describing a dissolution test almost always assumes that the tests been conducted are using these apparatuses.

The main objective of a dissolution test is to evaluate or predict dissolution characteristics of a product in vivo, mostly in humans. Often this link, or predictability aspect, is referred to as in vitro-in vivo co-relationship (IVIVC). Continue reading →

It is often debated as to which approach is better or more appropriate for calibration or standardization of the apparatuses. It appears that calibration may not be a critical or important step, at present. The reason being, even if the apparatuses (paddle and basket) are adequately calibrated using any of the two approaches, they still would show lack of relevance of results and provide very high variability in dissolution results.

It has been shown from experimental studies and computer simulation modeling that paddle and basket apparatuses provide poor hydrodynamics, thus results obtained from these apparatuses would be of limited value and use. As a results the calibration aspect becomes secondary.

It is often claimed that drug dissolution testing is a useful technique during the product development stage. Does this claim have merit? Let us explore.

A formulator prepares two or more formulations/products having different dissolution rates using commonly described dissolution test conditions. How would the formulator decide which product can be tested in humans? For this purpose the formulator needs to have some confidence in the predictability of the dissolution test for the behaviour of a product in humans. It is well known that current practices of dissolution testing do not provide such predictability, thus the testing cannot be used for product development. There are examples showing that products having differences in vitro results, provides overlapping in vivo results.

Then why do people suggest the use of dissolution testing for product development. Apparently, the suggestion is correct but not its interpretation. In principle, it is correct that dissolution tests should be reflective of in vivo results. However, success will depend on how a dissolution test is conducted and what type of instrument/apparatus is used. Presently, people invariably assume that dissolution testing means conducting a test using paddle and basket apparatus. The missing link here is that these apparatuses have never been validated to provide relevant in vivo conditions (environment) to predict in vivo results? Obviously, these apparatuses cannot provide relevant in vivo results. It is like saying that can a distance from point A to B, 1000 miles apart, be travelled in an hour by road. Of course, yes, but we need a car which would be able to run at a speed of 1000 miles/hour. Objective is fine but the practicality of achieving the objective is not. This is exactly what is happening with the current practices of drug dissolution testing, i.e., the objective is fine but means (paddle and basket apparatuses) to achieve the objective is not.

Thus, the common practices of dissolution testing fail to provide relevant in vivo results and will not provide relevant results at the product development stage.